Mouse mammary gland contains polyamine-dependent choline kinase, which catalizes the formation of the precursor for the membrane components. With the organ culture system, stimulation of choline kinase activity has been shown to be dependent on the actions of insulin and cortisol, the same combination of hormones that causes accumulation of rough endoplasmic reticulum. The hormonal stimulation of choline kinase activity appears to involve the action of spermidine, a polyamine which accumulates in the cells under the influence of cortisol and mimicks that effect of cortisol on milk-protein synthesis in culutred mouse mammary explants. Lithium ion at 2 to 20mM simulated the effects of insulin on cell-proliferation in mouse mammary gland in culture. Lithium ion, however, is incapable of substituting for the action of insulin in augmenting milk protein synthesis. The observed similarities of the response of mammary cells to lithium and insulin suggest the possible importance of cation(s) in the regulation of mammary cell proliferation. On the other hand, the observed inability of lithium to mimic the lactogenic effect of insulin indicates a specific function of the hormone in the functional differentiation of mammary cells.